Colchicine / Probenecid Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Gouty Arthritis

Chronic gouty arthritis complicated by frequent, recurrent acute attacks of gout:
Initial dose: 1 tablet orally once a day for 1 week
Maintenance dose: 1 tablet orally twice a day

Colchicine-probenecid should be continued at the dosage that will maintain normal serum urate levels.

Renal Dose Adjustments

Colchicine-probenecid has been used in patients with some renal dysfunction but dosage requirements may be increased. A daily dosage of 2 tablets orally may be adequate; however, if necessary, the daily dosage may be increased by 1 tablet every 4 weeks within tolerance (usually not greater than 4 tablets/day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not about 700 mg.

Colchicine-probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is 30 mL/minute or less.

Liver Dose Adjustments

Data not available

The possibility of increased colchicine toxicity in the presence of hepatic dysfunction should be considered.

Dose Adjustments

Colchicine-probenecid should be continued at the dosage that will maintain normal serum urate levels. When 6 months or more have passed without acute attacks and serum urate levels remain within normal limits, the daily dose of colchicine-probenecid may be reduced by 1 tablet every 6 months. The maintenance dose should not be decreased to the point where serum urate levels tend to rise.

Gastric intolerance may be indicative of overdosage and may be corrected by decreasing the dose.

Precautions

Colchicine-probenecid therapy should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, colchicine-probenecid may be continued with no dose adjustment; additional colchicine or other appropriate therapy should be used to control the acute attack.

Colchicine-probenecid is contraindicated in patients with known blood dyscrasias or uric acid kidney stones. The use of salicylates (in small or large doses) is contraindicated in patients on colchicine-probenecid.

Coadministration of colchicine with P-glycoprotein or potent CYP450 3A4 inhibitors is contraindicated in patients with renal or hepatic dysfunction.

Severe allergic reactions and anaphylaxis have been reported rarely. Most cases occurred within several hours after resuming therapy with colchicine-probenecid. Therapy should be discontinued if hypersensitivity reactions occur.

Colchicine administration may produce serious and possibly fatal systemic toxicity. Patients and health care professionals should be aware of the signs and risk factors of acute colchicine toxicity.

Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of colchicine-probenecid in gouty patients may be prevented by alkalization of the urine and liberal fluid intake. When alkali is administered, the patient's acid-base balance should be monitored.

Colchicine-probenecid should be used with caution in patients with a history of peptic ulcer. Colchicine should be used with caution in the elderly and in debilitated patients.

Colchicine-probenecid is contraindicated in pediatric patients less than 2 years of age. Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Colchicine-probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is 30 mL/minute or less.

Colchicine is not effectively removed by dialysis.

Other Comments

As uric acid tends to crystallize out of acidic urine, liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily) or potassium citrate (7.5 g daily) to maintain alkaline urine. Alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear (i.e., during the period when urinary excretion of uric acid is at a high level). Thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed.

Patients on methotrexate therapy may be at an increased risk of methotrexate toxicity if given probenecid. In animal studies, probenecid has increased plasma methotrexate levels leading to toxicity. If colchicine-probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored.

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